2B, β = 0 834, uncorrected p = 0 006,

2B, β = 0.834, uncorrected p = 0.006, CX-4945 q = 0.032). Although there appears to be an outlier in Fig. 2C (corresponding to the participant ranked 18), its influence was minimized

by converting all values to ranks (see Section 2). Pathways through pOTS-ITS, pOTS-pMTG, ITS-pSTG, pMTG-pSTG, and pMTG-AG were not significantly correlated with imageability effects. No reliable associations were found between pathway volumes and age, level of education, or behavioral effects of word frequency, consistency, letter length, the interaction of word frequency and consistency, or the interaction of consistency and imageability ( Table 1). The specificity of the findings to imageability JQ1 and not the other tested factors makes it unlikely that the findings are due to individual differences in ROI volumes or group differences in pathway volumes. In fact, imageability effects across participants did not significantly correlate with ROI volumes for any of the ROIs. Volumes for both the ROIs and the examined pathways are given for reference in Table 2. Overall, these findings (1) identify novel structural brain correlates underlying individual differences

in reading, and (2) reveal functional–anatomical pathways supporting the mapping between semantics and phonology in reading aloud. To situate these findings within the context of known major white matter pathways, we created an overlap image in Talairach space of the AG-pSTG pathways from each of the individual subjects, and did the same for the ITS-pMTG pathways. These PAK5 were thresholded so that only tracts co-occurring in at least 9 (50%) of the participants were displayed. Probabilistic maps of major known tracts from the Johns Hopkins

University (JHU) white matter atlas were also registered to Talairach space and thresholded at 50% (Hua et al., 2008). As can be seen in Fig. 3A, the AG-pSTG pathway encompassed the parieto-temporal branch of the superior longitudinal fasciculus (SLF-PT), while also extending beyond it. The SLF-PT may correspond to the posterior segment of the arcuate fasciculus as identified by Catani and Jones (2005). One difference between the SLF-PT and the current AG-pSTG pathway, however, is that the latter extends to the AG, while the SFL-PT appears to lie mainly in the posterior peri-Sylvian white matter. The ITS-pMTG pathway overlapped most closely with the inferior longitudinal fasciculus (ILF), though the course of the ILF had a longer extent in the anterior and posterior directions (Fig. 3B). Defining pathways using spherical ROIs near the ends of these known tracts as waypoints, however, did not yield significant correlations with imageability (for ILF: β = 0.758; for parieto-temporal branch of arcuate: β = 0.327; for fronto-temporal branch of arcuate: β = 0.566; all q > 0.1).

While Table 1 lists the minimum change that could be associated w

While Table 1 lists the minimum change that could be associated with biologically relevant endpoints, other field studies have reported much higher changes in observed parameters. For example, populations of white sucker (Catostomus commersoni) exposed to bleached kraft mill effluents had GSI, LSI and CF deviations of 30% or more relative to reference fish ( Mower et al., 2011). The power of the test, 1-β, is a third factor influencing the Ganetespib number of samples to collect. The convention in environmental sciences is

that power should be at least 0.80 ( Fairweather, 1991), i.e., there should be an 80% chance of detecting a difference between sites. The power of a test can be determined easily from calculations

using similar variables as the minimum sample size (G∗Power 3 can calculate power using a different set of instructions). Obviously, collecting the minimum number of samples will give low power and increase the chances of committing a Type II error (false negative: concluding there is no impact when in fact there was one). In a multi-sample analysis of variance, the power increases rapidly with the number of samples used. Consequently, if there is an opportunity to collect a few more fish at each site, the benefit of each additional fish can be calculated using the power equations. In the present case, the n required DAPT order has been calculated for a power of 0.80 and 0.95, as under many situations it is prudent to reduce the possibility of Type II error where possible. From the perspective of environmental management, a Type II error is far more serious than a Type I error. A Type I error can be seen as a false alarm which could trigger further environmental protective measures – it is only a question of time before the mistake is realized through additional sampling. In contrast, a Type II error leading to a conclusion of ‘no impact’ would result in no remediation measures being implemented, a possible

reduction in monitoring effort, and a continuing environmental deterioration. Thus, due to a lack of statistical power, there would be continued environmental degradation. The fourth factor affecting the minimum required sample size is Montelukast Sodium the variability of the parameter. Biomarkers can be notoriously variable. For example, the coefficients of variation of all parameters except CF ranged from 12.6% to 127% (Table 2), while the coefficient of variation for CF averaged 6.1%. If the variability within a sampling site is great, a larger sample size will be required to detect a given difference between means (Zar, 1996). Sources of variability for a given biomarker include individual (random) variability, systematic sampling error due to confounding factors, and analytical variability.

1 Annex 9 regulation: The wash water pH should comply with one of

1 Annex 9 regulation: The wash water pH should comply with one of the following requirements which should be recorded in the ETM-A or ETM-B as applicable: (I) The discharge wash water

should have a pH of no less than 6.5 measured at the ship’s overboard discharge with the exception that during manoeuvring and transit, the maximum difference between inlet and outlet of 2 pH units is allowed measured at the ship’s inlet and overboard discharge. The acronyms ETM-A and ETM-B refer to technical manuals from the manufacturer (EGC system – Technical Manual). The seawater pH varies approximately from 7.5 to 8.5 meaning that a discharge of fluid at a pH of 5.5 is permitted in certain conditions (e.g. north-eastern regions of the Baltic Sea) in the case of (I). However,

in the case of (II) there is no limit to the discharge pH as long as it recovers to a pH of 6.5 within a distance of 4 m from the nozzle. Regulatory compliance is demonstrated selleckchem by measuring the pH at a fixed depth and 4 m in front of the discharge port while the ship is held at rest with its engines running and driving the propeller. This means that an ambient flow will be present deviating the discharge in combination with buoyancy originating from the wash water’s contact with check details hot exhaust gases. The focus of this paper is on the pH recovery of scrubber discharges, however, in order to fully comply with the legislation the measurements of PAH (oil content), turbidity and temperature also need to be monitored and controlled. We will be addressing case (II) because it allows for a lower discharge pH and we also analyse the discharge deviation due to temperature and ambient flow up to 4 m from the nozzle. Wash water pH recovery depends in part on the chemical composition of seawater and on the amount of dilution. Seawater is a weak alkaline

buffer solution which contains a large number of dissolved salts (Drever, 1988), Carnitine palmitoyltransferase II some of which affect its pH. Alkaline buffer solutions resist changes to pH by absorbing hydrogen ions (H+) when small amounts of acid are added. The majority of the seawater buffering capacity comes from carbonate ( CO32-) and bicarbonate ( HCO3-) ions. Calcium carbonate (CaCO3) is a sparingly soluble alkaline salt that is very common in seawater, therefore, the seawater alkalinity is frequently estimated in calcium carbonate equivalent moles. Seawater’s buffering capacity is also influenced by temperature, depth, salinity and coastal runoffs. For example, glacial ice melting in the summer introduces fresh water into seawater reducing the acid buffering capacity. Typical values of seawater alkalinity around the globe range from 2200 to 2400 μmol/kg (Fig. 2a). In parts of the Baltic Sea, however, alkalinity is far lower at 800 μmol/kg (Fig. 2b). The brackish characteristic of the Baltic Sea is due to the large number of rivers flowing into it and the limited exchange with the North Sea.

The alignment of these transcripts showed a high identity (94%) f

The alignment of these transcripts showed a high identity (94%) for the signal peptide, propeptide and mature peptide. Sequence alignment of predicted protein also revealed a high structural conservation, showing a score of 96%. Besides this score, the propeptide sequence showed a deletion of a conserved Asp residue, which might reflect differences in the spectrum of biological activity (data not shown). The tryptophyllins were first isolated from P. dacnicolor ( Meneses et al., 2011), and they belong to a large family of peptides with a conserved Trp residue 3-Methyladenine clinical trial at position P2 of the active peptide, and a Pro residue at the N-terminal domain. Asynthetic replicate of tryptophyllin-1, a

member of this family, the peptide PdT-1,

was shown to be a potent myoactive agent, relaxing mammalian arterial smooth muscle and contracting selleck chemicals llc small intestinal smooth muscle ( Chen, 2004). We describe here two contigs and one singlet homologous to tryptophyllin. One of them TP01 showed similarity to sauvatide, which is a myotropic peptide from P. sauvagii ( Wang et al., 2009), whereas TP02 was similar to P. dacnicolortryptophyllin-1. The alignment of nucleotide sequences allowed observing 88% of similarity between TP01 and sauvatide, and 90% of similarity between TP02 and tryptophyllin-1. The singlet TP03 was 85% similar to aurein, a peptide with antimicrobial and antitumoral properties ( Rozek et al., 2000). Sequence comparison performed using BlastX showed that only TP01 has significant structural conservation that is typical of secreted peptides, mainly characterized by a signal peptide followed by a propeptide and a mature peptide

sequence. The open reading frames of the sequences corresponding to TP02 and the alignment of the deduced amino acid sequences are shown in Supplementary material Fig S3. Bradykinin-related peptides (BRPs) are similar to the nonapeptide Verteporfin bradykinin originally described by Rocha e Silva et al. (1949) as a potent vasodilator. These peptides are expressed in many living organisms, including wasps (Picolo et al., 2010) and anurans including some species ofPhyllomedusa genus ( Brand et al., 2006a and Brand et al., 2006b; Chen and Shaw, 2003; Thompson et al., 2006). A high structural diversity of BRPs in the skin secretions of frogs and toads was described ( Chen et al., 2011). The pharmacological effects induced by BRPs include antagonism of bradykinin effects on smooth muscle, vasodilatation, vasoconstriction, and hyperalgesia ( Conceição et al., 2009; Picolo et al., 2010; Zhou et al., 2009). Two singlet sequences showing similarity to BRPs, coined as BK01 and BK02, were found in our database. BlastX did not show any significant similarity to known sequences for these singlets suggesting also the variability of DNA sequences in addition to the structural peptides variability. Thus the transcripts of P. nordestina may represent new transcripts encoding BRPs.

As SRL has a long-half-life, C0 obtained 5–7 days after

t

As SRL has a long-half-life, C0 obtained 5–7 days after

the start of treatment or dosage change should be used this website to determine dose adjustments while 4 days at the most is needed for EVR owing to its shorter half-life. After the initial dose titration, weekly SRL C0 measurements during the first month, then every 2 weeks, have been recommended [55]. There are several assays available to measure blood mTOR inhibitor levels, with High-Pressure Liquid Chromatography coupled with Mass Spectrometry (HPLC/MS) being the most accurate and specific method. Immunoassay is also a reliable and more convenient alternative. It is important to know which assay is being used, as immunoassays may lead to overestimation of EVR and SRL concentrations as a result of cross-reactivity with metabolites [56]. Differences in immunosuppressive dosages and regimens among the studies make it difficult to determine the optimum dosing strategy for TAC with mTOR inhibitors. Therapeutic target ranges for TAC when

used in combination with EVR or SRL are not as yet established. It should be Cyclopamine remembered, however, that higher doses of mTOR inhibitors are required when administered with TAC than with CsA [44]. In general, there is little interaction between TAC and mTOR inhibitors, whereas interactions between CsA and mTOR inhibitors are more pronounced and result in higher blood levels of mTOR inhibitors [40] and [44]. Consequently, higher starting doses of EVR are needed when combined with low-dose TAC than with CsA to

prevent increased risk of rejection. In addition, careful concentration monitoring of both EVR and SRL is advisable when patients are switched between CNIs [34]. Autophagy activator The EVR/CsA interaction is one of the reasons twice-daily dosing is recommended for EVR. Clinical data on the use of EVR or SRL in TAC minimization strategies in renal transplantation are limited. Available evidence suggests that treatment with EVR allows early and substantial TAC minimization when used with basiliximab induction and corticosteroids. The lack of clear differentiation in TAC exposure between standard- and reduced-dose TAC groups in the US09 and ASSET studies highlights ongoing reluctance to reduce CNI exposure even in the presence of EVR. SRL has also been used successfully as part of a TAC-minimization strategy, resulting in similar efficacy and less nephrotoxicity when compared with SRL/standard TAC. However, comparative studies support the use of other regimens (e.g., SRL/MMF, MMF/TAC) over SRL/TAC in this population. The findings with SRL, however, reflect single-center experiences. AEs are common in all transplant patients receiving immunosuppressive therapy. Several safety concerns may arise from using an mTOR inhibitor and TAC minimization therapy.

After allowing the solution to stand at 4 °C for 12 h, the extent

After allowing the solution to stand at 4 °C for 12 h, the extent of aggregation was examined by chromatography on Sepharose CL-2B by monitoring fractions with the

uronic acid assay. A bovine articular aggrecan (A1960, Sigma–Aldrich, USA) was used as a reference. A previously described standard procedure was used for the measurement of 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity [21]. Briefly, 1 mL of DPPH (100 μM, Sigma–Aldrich, USA) in ethanol and 1 mL of antler CS fraction at different concentrations of CS (0.625–10 mg/mL on) in 100 mM Tris–HCl buffer (pH 7.4) were mixed. This reaction mixture was shaken and incubated for 20 min in the dark at room temperature. Epacadostat cost The absorbance was measured at 517 nm against a blank control (100 mM Tris–HCl buffer). Measurements were performed in triplicate over a 60-s period for each sample. The DPPH radical scavenging activity, namely the inhibitory ratio, was calculated using the following equation: scavenging activity (%) = (1 − Asample/Ablank) × 100, where Ablank is the absorbance of the blank. Lower absorbance of the reaction mixture indicates higher free radical scavenging activity. Ascorbic acid and butylated hydroxytoluene (BHT) (Sigma–Aldrich, selleck USA) were used as positive controls. Two CS from bovine cartilage (C6737, Sigma–Aldrich, USA) and shark cartilage (C4384, Sigma–Aldrich, USA) were used as reference CS.

The results were presented as the means of experiments performed in triplicate ± standard deviation. Moisture content in antler cartilaginous tissue was estimated from the loss of sample weight Teicoplanin by heating at 110 °C overnight. Uronic acid contents were determined by the original [8] and the carbazole reaction [13], using d-glucuronolactone as a standard. Sulfated GAG was analysed using the dimethylmethylene blue dye binding method [9]. A CS from shark cartilage was used as a standard GAG. The content of hydroxyproline

(reflecting that of collagen) was determined by hydrolysis in 6 N HCl at 110 °C for 20 h [26]. The content of collagen was calculated by multiplying the content of hydroxyproline by 7.46 (collagen contains 13.4 percent hydroxyproline). Sialic acid content was determined by the periodate-thiobarbituric acid reaction [31] after hydrolysis of samples in 0.1 N sulphuric acid at 80 °C for 1 h. Protein was determined using the Lowry method [16] using BSA as a standard. Analysis of amino acids of purified CS fraction was performed by HPLC after hydrolysis with 6 N HCl at 110 °C for 24 h as previously described [28]. All analyses were performed in triplicate, unless otherwise specified. The values were averaged and standard deviations (SD) were calculated. All data were analysed by one-way analysis of variance and Duncan’s multiple range tests using SPSS software (version 10 SPSS, Chicago, IL, USA). The results were considered significant at P < 0.05.

Although many researchers assume the temperature regime to be a s

Although many researchers assume the temperature regime to be a sensitive marker for the testing of climate changes, other characteristics ALK inhibitor such as the duration of the ‘biological summer’

(the period with temperatures > 10°C, Efremova & Palshin 2012) can be used as an important marker of climate change, because it determines the initial biomass growth rate and the reproduction rate (abundance) of aquatic organisms. The example of six lakes in Karelia from 1953 to 2009 shows that the duration of the ‘biological summer’ has increased by 12–23 days and that the trend of the prolongation of the ‘biological summer’ is positive (p < 0.05) ( Efremova & Palshin 2012). The majority of the lakes in East Fennoscandia are characterised by an increase in the ice-free period (Filatov www.selleckchem.com/Bcl-2.html et al. 2012). Earlier ice-melting in Lake Onega can result in a shift of the spring bloom period of diatoms. The negative correlation between the ice-free period and plankton characteristics (Chl a and N phytoplankton) may be explained by the predominance of large-sized diatoms (Tabellaria fenestrata and Aulacoseira islandica) in the summer phytoplankton. Chl a in these species is lower than in other algae (diatoms). The negative correlations between NAO, AO, precipitation

and zoobenthos abundance and biomass testify that nutrient and organic matter loads from the catchment area can increase together with the increase of precipitation in years with a positive NAO. In turn, eutrophication Cell press phenomena (hypoxia, H2S production etc.) can reduce the numbers of sensitive species (relict amphipods) and, conversely, favour eurybiotic taxa (oligochaetes). Oxygen depletion and higher temperatures accelerate nutrient release processes at the sediment-water

interface (Søndergaard et al. 2003) and increase the stress on aquatic organisms (Weider and Lampert, 1985, Saeger et al., 2000 and Wilhelm and Adrian, 2007), resulting in a decrease in their abundance. Significant correlations between climate indices, physical parameters in Petrozavodsk Bay, Lake Onega, and some characteristics of its biota (phytoplankton, zoobenthos) were found in this research. We conclude that global climate primarily determines the regional hydrological variables of a lacustrine ecosystem and its productivity level, whereas biotic characteristics are a reflection principally of the variability in the water temperature and the ice-free period, both of which determine the duration of the ‘biological summer’ (WT > 10°C). At the same time, the responses of biological communities and whole ecosystems to climate variability are complex and often difficult to recognise, especially in the case of large ecosystems with a long period of water exchange. We cordially thank Professor Nikolai N. Filatov, Dr Natalia M. Kalinkina for the valuable discussion and also Mrs Y.

Determination of the wave height after breaking takes place in th

Determination of the wave height after breaking takes place in the EPZ015666 following steps: • Let us consider, for example, a wave with parameters H0 = 0.3 [m] for the beginning of the storm (t = 0) and T = 6 [s]. Figure 6 shows the changes of the relative wave height HHbr as a function of distance from the shoreline, and Figure 7 presents the changes of parameters (25) of the mean sea level elevation during a storm. The changes of the characteristic points of the mean sea level elevation during a storm are summarised in Table 1. The table shows that during the storm, the height of a breaking wave (Hbr)

over shallowing water depth changes significantly, from 0.61 [m] at the beginning, to 2.78 [m] for time t = 12h, when the storm reaches its maximum. Also the place of wave breaking changes from 167.43 [m] with the smallest waves, to 219.49 [m], for the higest waves. As a result of this, extreme nonlinear values of the mean sea level elevation change in the following range: −0.044m≤ζbr≤−0.154mand0.14m≤ζmax≤0.56m. Furthermore, LGK-974 the surf zone width (Table 2, Figure 8) changes. As shown in Figure 3 the width is different for the linear (dependence (17)) and nonlinear relation (24). The raising of the mean water level due to the presence of waves causes an additional hydrostatic pressure in the surf zone. This pressure is a driver of water movement in the pore layer.

Massel (2001) presents a theoretical attempt to predict the groundwater circulation due to linear wave set-up. An analogous procedure is applied to the case when the boundary condition is not linear and the mean sea level is assumed after Dally et al. (1985) – see formula (24). The next step presents the results of calculation of pressure fields and the circulating of pore waters with the assumption of a nonlinear course of the mean sea level elevation. Figure 9 shows the distribution of pressure and streamlines for a nonlinear

mean sea level elevation. Two different systems of water circulation are generated as a result of pressure applied additionally to the bottom. On the left-hand side the impact of the positive pressure gradient driving water movement towards the shore is marked. This means that the pressure gradient is strong enough to overcome Methane monooxygenase the viscosity force in the boundary layer. On the right the second cell of circulation caused by the negative pressure gradient is shown. The line dividing the two systems is formed in the place where the stream function values are zero. This observation is confirmed by the shape of the velocity field in the porous layer (Figure 10). As seen in Figure 10 water penetrates into porous surfaces in the form of two circulation cells. In both cases, infiltration into the porous medium begins in the vicinity of the place where additionally applied pressure reaches its maximum value.

In 1976 using SCUBA divers they documented two spawning grounds:

In 1976 using SCUBA divers they documented two spawning grounds: near the town of Palanga and the village of Karklė (BaltNIIRH 1989). However, that mapping was supported only by 7 actual finds of herring eggs (3 off Palanga and 4 off Karklė) and was therefore relatively imprecise. Repeated BaltNIIRH surveys after the ‘Globe Assimi’ oil-tanker disaster in the port of Klaipėda in 1981, which resulted in a massive (16 000 tons) oil spill, showed that the spawning ground off Karklė (closer to the disaster site) had been destroyed (Koroliov CDK inhibitor 1991). Since then, no mapping of

the Baltic herring spawning grounds has been carried out. Although the patterns of Baltic herring spawning have been studied intensively in other Baltic Sea regions, the factors shaping its distribution are not fully understood. Although there are a few reports stating that spawning beds are often found close to the deeper areas (Kääriä learn more et al. 1988, 1997, Rajasilta et al. 1993), the precise relationship between bottom geomorphology and spawning beds has not been analysed. To do so, high resolution bathymetric data with modern analytical tools are needed. The aim of this study is to evaluate the current status of the Baltic herring spawning grounds in Lithuanian coastal waters and to assess the factors

determining their spatial distribution, with special emphasis on small-scale geomorphological features of the sea bed. This is important for gaining a better understanding of Baltic herring spawning patterns and for the better management of herring stocks and their restoration. The Lithuanian

coast in the south-eastern Baltic Sea is exposed to all westerly directions, with a wind fetch exceeding 200 km. Thymidine kinase The coastline is straight, with no inlets, islands or any other features providing shelter. In the southern part, along the Curonian spit, coastal bottom sediments are dominated by sand, while in the northern part they consist of a complex mosaic of moraine clay, large boulders, cobbles, pebbles, gravel and sand (Gulbinskas & Trimonis 1999). In general, Baltic herring do not spawn on soft substrates (Rajasilta et al. 1989, Kääriä et al. 1997), and no spawning events along the Curonian Spit have been registered. Therefore, only the northern part of the Lithuanian coast was investigated during this study. The average near-bottom salinity in the area ranges from 6 to 7.5 PSU, but may occasionally drop to less than 5 PSU (Daunys et al. 2007) as a result of freshwater inflows from the Curonian Lagoon. The hypereutrophic waters of the lagoon propagate into the sea, reducing underwater visibility from 3–6 m to 0–2 m (typically no more than 1 m) and inducing a faster rate of organic matter deposition on the bottom. Bottom biotopes in the study area are distributed according to depth and substrate availability (Olenin & Labanauskas 1994).

In these studies, the dosages used in Japan (alendronate 5 mg dai

In these studies, the dosages used in Japan (alendronate 5 mg daily/35 mg weekly; risedronate 2.5 mg daily/17.5 mg weekly) were half the dosage used outside Japan

find protocol (alendronate 10 mg daily/70 mg weekly; risedronate 5 mg daily/35 mg weekly) [2], [3], [4], [5] and [6]. The difference in oral bisphosphonate dosages between Japanese and subjects outside Japan suggested a difference in bioavailability between Japanese and non-Japanese individuals, although the reasons for this difference remain unknown [8]. Adherence to the treatment regimen is important for osteoporosis but there are a number of obstacles to adherence. Since osteoporosis is a chronic disease requiring long-term clinical management, some patients may have problems complying with medication instructions consistently and find them burdensome. Indeed, it has been reported that patients who are poorly adherent to bisphosphonate therapy Panobinostat molecular weight do not maintain the same level

of improvement in bone mineral density (BMD) [9], [10] and [11]. Moreover, non-adherence with antiresorptive therapy has been reported frequently and it has been reported to result in a 16–50% increased risk of fracture [9], [10], [11] and [12]. In Japan, a once-weekly regimen improved treatment adherence to bisphosphonates, which was a problem associated with once-daily products. Nevertheless, 20% or more patients stopped taking the drug after 6 months of treatment [13]. From the results of online surveys of Japanese dipyridamole patients and patients outside Japan taking bisphosphonates, it was shown that patients tended to prefer once-monthly products to once-daily or once-weekly products because of the lower frequency of administration [13], [14], [15], [16] and [17]. Furthermore, treatment

adherence with once-monthly and once-weekly dosage regimens has also been evaluated in clinical studies outside Japan, and once-monthly products provided improved treatment adherence compared with once-weekly products [14]. Monthly administration is expected to improve treatment adherence in Japanese patients receiving long-term bisphosphonate therapy who are having difficulty complying with daily or weekly dosage regimens [15], [18] and [19]. The aim of this randomized, double-blind study was to compare, in patients with involutional osteoporosis, the efficacy and tolerability of oral risedronate 2.5 mg once-daily with that of 75 mg once-monthly, which is 30 times larger than the recommended daily dose and half the monthly dose (150 mg) used outside Japan [7]. This is consistent with the daily and weekly doses (2.5 mg and 17.5 mg, respectively) used in Japan, being half the daily and weekly doses (5 mg and 35 mg, respectively) used outside Japan.